ABSTRACT
In the present study, the neuroprotective effect of 5-hydroxy-6,7,4'-trimethoxyflavone (flavone 1), a natural flavone, was investigated in comparison with another flavone, 5,7,4'-trihydroxyflavone (flavone 2) on the hippocampus of amyloid beta (Aß)-injected rats. Rats were treated with the 2 flavones (1 mg/kg/d) for 1 week before Aß injection. Seven days after Aß administration, memory function of rats was assessed in a passive avoidance test (PAT). Changes in the levels of mitochondrial transcription factor A (TFAM), peroxisome proliferator-activated receptor γ coactivator 1 α (PGC-1α), phospho-adenosine monophosphate (AMP)-activated protein kinase (pAMPK), AMPK, phospho-cAMP-responsive element-binding protein (CREB), CREB, and nuclear respiratory factor 1 (NRF-1) proteins were determined by Western blot analysis. Our results showed an improvement in memory in rats pretreated with flavonoids. At the molecular level, phosphorylation of CREB, known as the master modulator of memory processes, increased. On the other hand, the level of mitochondrial biogenesis factors, PGC-1α and its downstream molecules NRF-1 and TFAM significantly increased by dietary administration of 2 flavones. In addition, flavone 1 and flavone 2 prevented mitochondrial swelling and mitochondrial membrane potential reduction. Our results provided evidence that flavone 1 is more effective than flavone 2 presumably due to its O-methylated groups. In conclusion, it seems that in addition to classical antioxidant effect, flavones exert part of their protective effects through mitochondrial biogenesis.
Subject(s)
Alzheimer Disease/prevention & control , Dietary Supplements , Disease Models, Animal , Flavones/therapeutic use , Neuroprotective Agents/therapeutic use , Nootropic Agents/therapeutic use , Transcription Factors/agonists , Alzheimer Disease/metabolism , Animals , Avoidance Learning , Behavior, Animal , Cyclic AMP Response Element-Binding Protein/agonists , Cyclic AMP Response Element-Binding Protein/metabolism , Hippocampus/metabolism , Male , Memory , Mitochondrial Dynamics , Mitochondrial Proteins/agonists , Mitochondrial Proteins/metabolism , Nerve Tissue Proteins/agonists , Nerve Tissue Proteins/metabolism , Neurons/metabolism , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha , Phosphorylation , Protein Processing, Post-Translational , Rats, Wistar , Transcription Factors/metabolismABSTRACT
OBJECTIVES: We evaluated the acetylcholinesterase (AChE) inhibitory and potential antioxidant effects of Salvia sahendica extract to investigate whether these molecules are involved in learning and memory improvement in rats injected with fibrillar amyloid beta (Aß) peptide in the CA1 region of their hippocampus. METHODS: Rats were fed with S. sahendica (100 mg/kg/day) for 1 week before Aß injection. Western blot analysis and enzymatic assays were carried out 7 days after injections. KEY FINDINGS: Our results indicated that S. sahendica extract decreased AChE activity. Besides, S. sahendica prevented reduction in the level of nuclear respiratory factor-1 and mitochondrial transcription factor A (TFAM). Our data indicated the lack of sensitivity in citrate synthase and reduction in the activity of malate dehydrogenase in the presence of Aß that was prevented with S. sahendica consumption. Pretreatment with S. sahendica extract impeded reduction of glutathione redox ratio, catalase and superoxide dismutase activity, while decreased the malondialdehyde level. CONCLUSIONS: Based on the importance of AChE activity inhibition and increased TFAM level in the prevention of cognitive impairment, the use of S. sahendica could open a new protective issue in therapeutic fields of neurodegenerative disease.